作为表皮生长因子受体和 CDK4/ 环素 D1 双重抑制剂的新型吡啶嘧啶衍生物：合成、生物筛选和分子建模。

IF 3.2 4区医学 Q3 CHEMISTRY, MEDICINAL Future medicinal chemistry Pub Date : 2024-08-17 Epub Date: 2024-07-18 DOI:10.1080/17568919.2024.2366147

Fatma Ma Krakisha, Dina Ia Othman, Walaa M El Husseiny, Magda Na Nasr

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引用次数: 0

摘要

目的：设计、合成了一系列吡啶嘧啶衍生物 5-20，并利用四种恶性细胞对其抗肿瘤活性进行了研究。材料与方法：使用宫颈癌（HeLa）、肝癌（HepG-2）、乳腺癌（MCF-7）和结肠癌（HCT-166）细胞以及正常人肺成纤维细胞（WI-38）测定细胞毒性。结果发现吡唑-1-基吡啶嘧啶衍生物 5 是对 Hela、MCF-7 和 HepG-2 这三种恶性细胞最有效的化合物，其 IC50 值与标准多柔比星相比分别为 9.27、7.69 和 5.91 μM。此外，化合物 5 和 10 对细胞周期蛋白依赖性激酶（CDK4/细胞周期蛋白 D1）和表皮生长因子（EGFR）酶有良好的抑制作用。

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New pyridopyrimidine derivatives as dual EGFR and CDK4/cyclin D1 inhibitors: synthesis, biological screening and molecular modeling.

Aim: A series of pyridopyrimidine derivatives 5-20 was designed, synthesized and examined for antitumor activity using four types of malignant cells.Materials & methods: Cervical cancer (HeLa), hepatic cancer (HepG-2), breast cancer (MCF-7) and colon cancer (HCT-166) cells, as well as normal human lung fibroblast cells (WI-38) were used to determine the cytotoxicity.Results: Pyrazol-1-yl pyridopyrimidine derivative 5 was found to be the most active compound against three malignant cells Hela, MCF-7 and HepG-2 with IC₅₀ values of 9.27, 7.69 and 5.91 μM, respectively, related to standard Doxorubicin. Moreover, compounds 5 and 10 showed good inhibition against cyclin dependent kinase (CDK4/cyclin D1) and epidermal growth factor (EGFR) enzymes.

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来源期刊

Future medicinal chemistry CHEMISTRY, MEDICINAL-

CiteScore

5.80

自引率

2.40%

发文量

118

审稿时长

4-8 weeks

期刊介绍： Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.